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Immunotargeting Chemotherapy of Gastrointestinal Carcinoma using Monoclonal Antibody-Drug Conjugates

Research Project

Project/Area Number 60480308
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

TAKAHASHI Toshio  Kyoto Prefectural University of Medicine, 第一外科, 教授 (50079828)

Co-Investigator(Kenkyū-buntansha) YAMAGUCHI Toshiharu  Kyoto Prefectural University of Medicine, 第一外科, 助手 (90111327)
荻田 修平  京都府立医科大学, 小児疾患研究施設, 講師 (20128698)
Project Period (FY) 1985 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1986: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1985: ¥3,100,000 (Direct Cost: ¥3,100,000)
KeywordsMonoclonal Antibody / Conjugates / Clorectal Cancer / Gastric Cancer / Clinical Application / Targeting Cahemotheraphy / 化学療法 / ターゲッテング療法 / スキルス胃癌 / ネオカルチノスタチン / 迅速病理診断 / 癌のミサイル療法 / 制癌剤結合抗体
Research Abstract

Monoclonal antibody-drug coujugates were applied as a clinical trial for patients who,based on the experimental study,had colorectal cancer. Monoclonal antibody A7, from a mouse splenocyte immunized against human colon cancer,was used as a drug carrier for colon cancer. The anti-cancer drugs mitomycin C(MMC)and neocarzinostatin (NCS)were bound covalently to A7 to from the conjagates A7-MMC and A7-NCS. The in vitro cytotoxic effects of the conjugates on SW1116 were stronger than those on free MMC or NCS. The conjugate A7-NCS, when administered to nude nice, brought about the highest NCS tumor concentration, whereas normal immunoglogulin G (IgG)-NCS distributed evenly in all tissues The conjugates showed a strong antitumor effect on colon cancer transplanted into nude mice. Forty-one patients with colorectal cancer, including ten patients with postoperative metastasis, were given A7-NCS. The immunoperoxidase and drug concentration studies of the resected specimens showed that NCS was localized specifically in cancer. Patients receiving the conjugate did not experience serious adverse effects. Of the eight patients with postoperative liver metastasis, three showed evidence of tumor reduction on computed tomograghy (CT)scan and three claimed pain felief. The conjugate did not benefit patients with multiple lung metastasis or peritoneal metastasis.

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 北村和也: 医学のあゆみ. 142. 503-504 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 高橋俊雄: 京都府立医大誌. 96. 261-269 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 高橋俊雄: 癌と化学療法. 14Part II. 931-937 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kotanagi, H.: Jpn. J. Sury.17. (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yokota. T.: Gastroent. Jpn.22. 565-570 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Takahashi, T.: Cancer. 61. 881-888 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] H,Kotanagi: "A monoclonal antibody against human colon cancers." Tohoku J. exp. Med.148. 353-360 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] H,Kotanagi: "Patent effect of the monoclonal antibody-mitomycin C conjugate on human colon cancers" Jpn. J. Surg.17. (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T,Yokota: "Monoclonal antibodies against human scirrhous carcinoma of the stomach" Gastroent Jpn.22. 565-570 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T,Takahashi: "Clinical application of monoclonal antibodydrug conjugates for immunotargeting chemotherapy of colorectal carcinoma" Cancer. 61. 881-888 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T,Takahashi: Excerpta Medica. Targetting chemotherepy using monoclonal antibody-drug conjugates for colorectal earlinoma. Cancer chemotherapy, challinges for the future, 345 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 高橋俊雄: 臨床外科. 41. 83-85 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 高橋俊雄: 新薬事報. 1380. 13-14 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 山口俊晴: 京都医学会誌. 33. 53-57 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 小棚木均: Tohoku Journal of Experimtntal Medicine. 148. 353-360 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 高橋俊雄: 日本外科学会雑誌. 87. 1000-1004 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 横田隆: 臨床科学. 22. 867-871 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 高橋俊雄: "癌における腫瘍マーカー外科卒後教育セミナー30" 中外医学社, 117-128 (1986)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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